Somatostatin is a tetradecapeptide having the structure: ##STR1## and has the properties of inhibiting the release of growth hormone, inhibiting the release of insulin and glucagon and reducing gastric secretion. Somatostatin itself has a short duration of action because it is inactivated, inter alia, by aminopeptidases and carboxypeptidases present in vivo. This problem of the short duration of action has been partially solved in the prior art by preparing derivatives of somatostatin which have low solubility, thus attaining a slow release on subcutaneous injection. Once dissolved, however, the derivatives are no more stable to inactivation by aminopeptidases and carboxypeptidases than somatostatin itself.
The present invention provides bicyclic somatostatin analogs which preferentially inhibit the release of growth hormone without affecting the level of gastric secretions or without affecting the level of gastric secretions, insulin and glucagon and thus have a more selective biological activity than somatostatin. The present analogs also have a longer duration of action than somatostatin because of their bicyclic structure. The present invention provides a novel method for preparing said analogs.